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Lectin

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Lateral hemagglutinine

Lectins are carbohydrate-binding proteins, macromolecules that are highly specific for sugar moieties. Lectins should neither be confused with glycoproteins (proteins containing sugar chains or residues), lecithins (fatty substances in animals and plants), nor leptin (the regulator of appetite and hunger, metabolism, and behavior).

Long before a deeper understanding of their numerous biological functions, the plant lectins, also known as phytohemagglutinins, were noted for their particular high specificity for foreign glycoconjugates (e.g. those of fungi, invertebrates, and animals).[1] and used in biomedicine for blood cell testing and in biochemistry for fractionation.

Lectins perform recognition on the cellular and molecular level and play numerous roles in biological recognition phenomena involving cells, carbohydrates, and proteins.[2][3] Lectins also mediate attachment and binding of bacteria and viruses to their intended targets. For example, it is hypothesized that some hepatitis C viral glycoproteins attach to C-type lectins on the host cell surface (liver cells) for infection.[4]

Lectins may be disabled by specific mono- and oligosaccharides, which bind to ingested lectins from grains, legume, nightshade plants and dairy; binding can prevent their attachment to the carbohydrates within the cell membrane.[5] Some lectins may be powerful toxins as for instance ricin, and others have been incorporated into genetically engineered crops to transfer traits, such as resistance to pests and resistance to herbicides.

Etymology

Table of the major lectins [6]
  Lectin Symbol Lectin name Source ligand motif
Mannose binding lectins
ConA Concanavalin A Canavalia ensiformis α-D-mannosyl and α-D-glucosyl residues

branched α-mannosidic structures (high α-mannose type, or hybrid type and biantennary complex type N-Glycans)

LCH Lentil lectin Lens culinaris Fucosylated core region of bi- and triantennary complex type N-Glycans
GNA Snowdrop lectin Galanthus nivalis α 1-3 and α 1-6 linked high mannose structures
Galactose / N-acetylgalactosamine binding lectins
RCA Ricin, Ricinus communis Agglutinin, RCA120 Ricinus communis Galβ1-4GalNAcβ1-R
PNA Peanut agglutinin Arachis hypogaea Galβ1-3GalNAcα1-Ser/Thr (T-Antigen)
AIL Jacalin Artocarpus integrifolia (Sia)Galβ1-3GalNAcα1-Ser/Thr (T-Antigen)
VVL Hairy vetch lectin Vicia villosa GalNAcα-Ser/Thr (Tn-Antigen)
N-acetylglucosamine binding lectins
WGA Wheat Germ Agglutinin, WGA Triticum vulgaris GlcNAcβ1-4GlcNAcβ1-4GlcNAc, Neu5Ac (sialic acid)
N-acetylneuraminic acid binding lectins
SNA Elderberry lectin Sambucus nigra Neu5Acα2-6Gal(NAc)-R
MAL Maackia amurensis leukoagglutinin Maackia amurensis Neu5Ac/Gcα2,3Galβ1,4Glc(NAc)
MAH Maackia amurensis hemoagglutinin Maackia amurensis Neu5Ac/Gcα2,3Galβ1,3(Neu5Acα2,6)GalNac
Fucose binding lectins
UEA Ulex europaeus agglutinin Ulex europaeus Fucα1-2Gal-R
AAL Aleuria aurantia lectin Aleuria aurantia Fucα1-2Galβ1-4(Fucα1-3/4)Galβ1-4GlcNAc,

R2-GlcNAcβ1-4(Fucα1-6)GlcNAc-R1

The name "lectin" is derived from the Latin word legere, meaning, among other things, "to select".

History

Although they were first discovered more than 100 years ago in plants, now lectins are known to be present throughout nature. It is generally believed that the earliest description of a lectin was given by Peter Hermann Stillmark in his doctoral thesis presented in 1888 to the University of Dorpat. Stillmark isolated ricin, an extremely toxic hemagglutinin, from seeds of the castor plant (Ricinus communis).

The first lectin to be purified on a large scale and available on a commercial basis was concanavalin A, which is now the most-used lectin for characterization and purification of sugar-containing molecules and cellular structures. The legume lectins are probably the most well-studied lectins.

Biological functions

Most lectins do not possess enzymatic activity. Lectins occur ubiquitously in nature. They may bind to a soluble carbohydrate or to a carbohydrate moiety that is a part of a glycoprotein or glycolipid. They typically agglutinate certain animal cells and/or precipitate glycoconjugates.

An oligosaccharide (shown in grey) bound in the binding site of a plant lectin (Griffonia simplicifolia isolectin IV in complex with the Lewis b blood group determinant); only a part of the oligosaccharide (central, in grey) is shown for clarity

Functions in animals

Lectins serve many different biological functions in animals, from the regulation of cell adhesion to glycoprotein synthesis and the control of protein levels in the blood. They also may bind soluble extracellular and intercellular glycoproteins. Some lectins are found on the surface of mammalian liver cells that specifically recognize galactose residues. It is believed that these cell-surface receptors are responsible for the removal of certain glycoproteins from the circulatory system.

Another lectin is a receptor that recognizes hydrolytic enzymes containing mannose-6-phosphate, and targets these proteins for delivery to the lysosomes. I-cell disease is one type of defect in this particular system.

Lectins also are known to play important roles in the immune system. Within the innate immune system lectins such as the MBL, the mannan-binding lectin, help mediate the first-line defense against invading microorganisms. Other lectins within the immune system are thought to play a role in self-nonself discrimination and they likely modulate inflammatory and autoreactive processes.[7] Intelectins (X-type lectins) were shown to bind microbial glycans and may function in the innate immune system as well.

Functions in plants

Leucoagglutinin, a toxic phytohemagglutinin found in raw Vicia faba

The function of lectins in plants (legume lectin) is still uncertain. Once thought to be necessary for rhizobia binding, this proposed function was ruled out through lectin-knockout transgene studies.[8]

The large concentration of lectins in plant seeds decreases with growth, and suggests a role in plant germination and perhaps in the seed's survival itself. The binding of glycoproteins on the surface of parasitic cells also is believed to be a function. Several plant lectins have been found to recognize non-carbohydrate ligands that are primarily hydrophobic in nature, including adenine, auxins, cytokinin, and indole acetic acid, as well as water-soluble porphyrins. It has been suggested that these interactions may be physiologically relevant, since some of these molecules function as phytohormones.[9]

Use in science, medicine, and technology

Use in medicine and medical research

Purified lectins are important in a clinical setting because they are used for blood typing.[10] Some of the glycolipids and glycoproteins on an individual's red blood cells can be identified by lectins.

  • A lectin from Dolichos biflorus is used to identify cells that belong to the A1 blood group.
  • A lectin from Ulex europaeus is used to identify the H blood group antigen.
  • A lectin from Vicia graminea is used to identify the N blood group antigen.
  • A lectin from Iberis amara is used to identify the M blood group antigen.
  • A lectin from coconut milk is used to identify Theros antigen.
  • A lectin from Dorex is used to identify R antigen.

In neuroscience, the anterograde labeling method is used to trace the path of efferent axons with PHA-L, a lectin from the kidney bean.[11]

A lectin (BanLec) from bananas inhibits HIV-1 in vitro.[12] Achylectins, isolated from Tachypleus tridentatus, show specific agglutinating activity against human A-type erythrocytes. Anti-B agglutinins such as anti-BCJ and anti-BLD separated from Charybdis japonica and Lymantria dispar, respectively, are of value both in routine blood grouping and research.[13]

Use in studying carbohydrate recognition by proteins

Lectin histochemistry of fish muscles infected by a Myxozoa

Lectins from legume plants, such as PHA or concanavalin A, have been used widely as model systems to understand the molecular basis of how proteins recognize carbohydrates, because they are relatively easy to obtain and have a wide variety of sugar specificities. The many crystal structures of legume lectins have led to a detailed insight of the atomic interactions between carbohydrates and proteins.

Use as a biochemical tool

Concanavalin A and other commercially available lectins have been used widely in affinity chromatography for purifying glycoproteins.[14]

In general, proteins may be characterized with respect to glycoforms and carbohydrate structure by means of affinity chromatography, blotting, affinity electrophoresis, and affinity immunoelectrophoreis with lectins as well as in microarrays, as in evanescent-field fluorescence-assisted lectin microarray.[15]

Use in biochemical warfare

One example of the powerful biological attributes of lectins is the biochemical warfare agent ricin. The protein ricin is isolated from seeds of the castor oil plant and comprises two protein domains. Abrin from the jequirity pea is similar:

  • One domain is a lectin that binds cell surface galactosyl residues and enables the protein to enter cells
  • The second domain is an N-glycosidase that cleaves nucleobases from ribosomal RNA, resulting in inhibition of protein synthesis and cell death.

Toxicity

Digestion and immune distress

Foods with high concentrations of lectins, such as beans, cereal grains, seeds, nuts, and potatoes, may be harmful if consumed in excess in uncooked or improperly-cooked form. Adverse effects may include nutritional deficiencies, and immune (allergic) reactions.[16] Possibly, most effects of lectins are due to gastrointestinal distress through interaction of the lectins with the epithelial cells of the gut. A recent in vitro study has suggested that the mechanism of lectin damage may occur by interfering with the repair of already-damaged epithelial cells.[17]

Lectins are considered another major family of protein antinutrients (ANCs), which are specific sugar-binding proteins exhibiting reversible carbohydrate-binding activities. Lectins are similar to antibodies in their ability to agglutinate red blood cells.

The toxicity of lectins has been identified by consumption of food with high lectin content, which may lead to diarrhea, nausea, bloating, and vomiting.

Many legume seeds have been proven to contain high lectin activity, termed hemagglutinating activity. Soybean is the most important grain legume crop in this category. Its seeds contain high activity of soybean lectins (soybean agglutinin or SBA). SBA is able to disrupt small intestinal metabolism and damage small intestinal villi via the ability of lectins to bind with brush border surfaces in the distal part of small intestine.[citation needed]

Heat processing can reduce the toxicity of lectins, but low temperature or insufficient cooking may not completely eliminate their toxicity, as some plant lectins are resistant to heat.

Lectin and leptin resistance

Lectin may cause leptin resistance, affecting its functions (signal have high levels of leptin and several effects gathering to protect from lipid overload), as indicated by studies on effects of single nucleotide polymorphisms on the function of leptin and the leptin receptor.[18] Such leptin resistance may translate into diseases, notably it could be responsible for obesity in humans who have high levels of leptin.

Lectin may involve in pattern recognition and pathogen elimination in the innate immunity of vertebrates including fishes.[19]

See also

References

  1. ^ Handbook of Plant Lectins: Properties and Biomedical Applications. John Wiley & Sons. March 30, 1998. pp. 7–8. ISBN 978-0-471-96445-2. Retrieved 18 April 2013. {{cite book}}: Unknown parameter |authors= ignored (help)
  2. ^ "Cell-to-Cell Binding Induced by Different Lectins". Journal of Cell Biology. 65 (2). Rockefeller University Press: 247–257. May 1, 1975. doi:10.1083/jcb.65.2.247. PMC 2109424. PMID 805150. {{cite journal}}: Unknown parameter |authors= ignored (help)
  3. ^ Bradley S. Schneider, ed. (April 2, 2013). "Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors". PLoS ONE. 8 (4 specific e code=e60838): e60838. doi:10.1371/journal.pone.0060838. PMC 3614905. PMID 23573288. {{cite journal}}: Unknown parameter |authors= ignored (help)CS1 maint: unflagged free DOI (link)
  4. ^ "Hepatitis C Virus Molecular Clones and Their Replication Capacity in Vivo and in Cell Culture". Virus Research. 127 (2). Elsevier: 195–207. 2007. doi:10.1016/j.virusres.2007.02.022. PMID 17428568. {{cite journal}}: Unknown parameter |authors= ignored (help)
  5. ^ "THE LECTIN STORY".
  6. ^ "Lectin list" (PDF). Interchim. 2010. Retrieved 2010-05-05.
  7. ^ Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB (2015). "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity". J Autoimmun. 57 (6): 1–13. doi:10.1016/j.jaut.2014.12.002. PMC 4340844. PMID 25578468.
  8. ^ Oldroyd, Giles E.D.; Downie, J. Allan (2008). "Coordinating Nodule Morphogenesis with Rhizobial Infection in Legumes". Annual Review of Plant Biology. 59: 519–46. doi:10.1146/annurev.arplant.59.032607.092839. PMID 18444906.
  9. ^ Komath SS, Kavitha M, Swamy MJ (March 2006). "Beyond carbohydrate binding: new directions in plant lectin research". Org. Biomol. Chem. 4 (6): 973–88. doi:10.1039/b515446d. PMID 16525538.
  10. ^ Sharon, N.; Lis, H (2004). "History of lectins: From hemagglutinins to biological recognition molecules". Glycobiology. 14 (11): 53R–62R. doi:10.1093/glycob/cwh122. PMID 15229195.
  11. ^ Carlson, Neil R. (2007). Physiology of behavior. Boston: Pearson Allyn & Bacon. ISBN 0-205-46724-5.
  12. ^ Swanson, M. D.; Winter, H. C.; Goldstein, I. J.; Markovitz, D. M. (2010). "A Lectin Isolated from Bananas is a Potent Inhibitor of HIV Replication". Journal of Biological Chemistry. 285 (12): 8646–55. doi:10.1074/jbc.M109.034926. PMC 2838287. PMID 20080975.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  13. ^ Viswambari Devi, R.; Basilrose, M. R.; Mercy, P. D. (2010). "Prospect for lectins in arthropods". Italian Journal of Zoology. 77 (3): 254–260. doi:10.1080/11250003.2010.492794.
  14. ^ "Immobilized Lectin".
  15. ^ Glyco Station, Lec Chip, Glycan profiling technology
  16. ^ Cordain, Loren; Toohey, L.; Smith, M. J.; Hickey, M. S. (2007). "Modulation of immune function by dietary lectins in rheumatoid arthritis". British Journal of Nutrition. 83 (3): 207–17. doi:10.1017/S0007114500000271. PMID 10884708.
  17. ^ Miyake K, Tanaka T, McNeil PL (2007). Steinhardt, Richard (ed.). "Lectin-Based Food Poisoning: A New Mechanism of Protein Toxicity". PLoS ONE. 2 (1): e687. doi:10.1371/journal.pone.0000687. PMC 1933252. PMID 17668065.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  18. ^ Jönsson, Tommy; Olsson, Stefan; Ahrén, Bo; Bøg-Hansen, Thorkildc; Dole, Anita; Lindeberg, Staffan (2005). "Agrarian diet and diseases of affluence--do evolutionary novel dietary lectins cause leptin resistance?". BMC Endocrine Disorders. 5: 10. doi:10.1186/1472-6823-5-10. PMC 1326203. PMID 16336696.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  19. ^ Arasu, Abirami; Kumaresan, Venkatesh; Sathyamoorthi, Akila; Palanisamy, Rajesh; Prabha, Nagaram; Bhatt, Prasanth; Roy, Arpita; Thirumalai, Muthukumaresan Kuppusamy; Gnanam, Annie J.; Pasupuleti, Mukesh; Marimuthu, Kasi; Arockiaraj, Jesu (2013). "Fish lily type lectin-1 contains β-prism architecture: Immunological characterization". Molecular Immunology. 56 (4): 497–506. doi:10.1016/j.molimm.2013.06.020. PMID 23911406.

Further reading

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